NO133446B - - Google Patents

Description

The invention relates to analogous methods for the production of bis-basic ethers of 2,6- and 2,7-dihydroxyanthraquinones with the general formula:

where R 1 and R 2, which are never the same, are hydrogen or the group where A is a straight-chain alkylene group of 2 or 3 carbon atoms and each R and R are hydrogen, an alkyl group of 1-3 carbon atoms or where R 3 and R 4 together with the nitrogen atom to which they are attached form a pyrrolidine, piperidine or morpholine ring. This invention encompasses both the base as represented by formula 1 and pharmaceutically acceptable acid salts of the base. As can be seen from formula 1 and the description, the compounds may have a structure in which R"<*>", in the 7-position, is hydrogen and R 2, in the 6-position, is the group as shown more fully by formula Ia or where R-*-, in the 7-position, is the group and R 2 , in the 6-position, is hydrogen as shown in formula Ib

where R 3 , R 4 and A have the previously stated meanings.

As examples of groups which A can represent in the compounds produced according to the present invention, ethylene and trimethylene can be mentioned. As examples of groups that R and R 4 can represent in the compounds according to the present invention, mention may be made of hydrogen, methyl, ethyl, propyl and iso-propyl and the saturated monocyclic heterocyclic groups, which R 1 and R 4 can represent together with the nitrogen atom , to which they are attached, are pyrrolidine, piperidino and morpholino.

The pharmaceutically acceptable acid addition salts of the basic compounds which are prepared according to the invention,

are those of any inorganic or organic acids. Examples of suitable acids for the production of salts include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acids and the like as well as organic carboxylic acids,

for example citric acid, malic acid, glycerol acid, lactic acid, tartaric acid, malonic acid, succinic acid, maleic acid and fumaric acid.

The compounds produced according to the present invention are used as active ingredients in antiviral compositions. The compounds prepared according to the present invention can be administered to a host to prevent, inhibit, resist or suppress infections by: pivornavirus, e.g. Encephalomyocarditis, myxovirus, e.g. Influenza B/Mass., arbovirus, e.g. Vesicular Stomatitis, ppxvirus, e.g. Vaccinia, IHD and herpes viruses, e.g. Herpes simplex. When the administration is carried out before the infection, i.e. prophylactically, it is preferred that the administration takes place within 0-48 hours before infection of the host with the pathogenic virus. When the administration takes place therapeutically to inhibit an infection, it is preferred that the administration takes place within 1 to 2 days after infection with the pathogenic virus.

The dose unit administered will depend on the virus for which treatment or prophylaxis is desired, the type of host animal, its age, health, weight, degree of infection, any type of other treatment, the frequency of the treatment and the intended effect. For example, the dose levels of the administered active ingredient can be: intravenously, 0.1 - 10 mg/kg, intraperitoneally, 0.1 - 50 mg/kg, subcutaneously, 0.1 - 250 mg/kg, orally, 0.1 - 500 mg/kg and preferably 1 - 250 mg/kg, intra-nasal instillation 0.1 - 10 mg/kg, and aerosol 0.1 - 10 mg/kg body weight.

Particular preferred compounds produced according to the invention are 2,7-bis [2-(diethylamino)-ethoxy]-anthraquinone and 2,6-bis-(2-piperidinoethoxy)-anthraquinone as these exhibit stronger antiviral activity when administered orally or subcutaneously than the other compounds produced according to the invention. These compounds also have higher LD^Q values and thus a better therapeutic index.

The compounds prepared according to the invention may be administered dissolved or suspended in any conventional non-toxic pharmaceutically acceptable carrier of such a type as may be taken orally, applied intranasally, orally or parenterally. Any suitable carrier can be used, e.g. a 15% aqueous hydroxyethylcellulose solution.

The antiviral activity of the compounds prepared according to the present invention was measured by well-known tests. In one type of an in vivo test, mice were treated with doses of the antiviral compositions according to the present invention, where the administration was carried out before and after infection. It was found that the infected mice treated with the agents survived within the experimental period of 9 to 10 days.

According to the present invention, the new bis-basic ethers of 2,6- and 2,7-dihydroxyanthraquinones can be prepared by different methods, for example according to the methods described in the special examples.

In the reaction scheme shown above which illustrates the present method, the starting material (II) is either 2,6-dihydroxyanthraquinone, i.e. anthraflavonic acid, which is commercially available, or 2,7-dihydroxyanthraquinone, i.e. anthraisoflavonic acid, which can be prepared according to the method of J. Hall and A.G. Perkin, J. Chem. Soc. (London), 123, 2036 (1923).

Examples of typical haloalkylamines (VIII) which can be used can be mentioned N,N-diethyl-2-chloroethylamine, N,N-dimethyl-3-chloropropylamine and N-(2-chloroethyl)-piperidine.

As examples of typical dihaloalkanes (III) which can be used, 1-bromo-2-chloroethane and 1,3-dibromopropane can be mentioned. Examples of amines (V) which can be used are primary amines, such as methylamine and ethylamine or secondary amines such as dimethylamine and diisopropylamine.

As examples of typical halogenalkanols (VI) which can be used, 2-chloroethanol, 2-bromoethanol, 3-chloropropanol and 3-bromopropanol can be mentioned.

In the reaction scheme shown above, the base used can be any base, for example sodium hydroxide, potassium hydroxide, sodium methoxide, sodium hydride, sodium amide, sodium carbonate or potassium carbonate.

The reaction can be carried out either in the presence or absence of a suitable solvent. Examples of suitable solvents that can be used as reaction medium in the reactions shown above include: aromatic hydrocarbons, such as benzene, toluene and xylene, halogenated aromatic hydrocarbons such as chlorobenzene and other aprotic solvents such as N,N-dimethylformamide, N ,N-dimethylacetamide and dimethylsulfoxide, alcohols such as ethanol, isopropanol and butanol, ethers such as tetrahydrofuran and dioxane, ketones such as acetone and butanone, water or suitable mixtures of such solvents.

In preparations using either sodium methoxide, sodium hydride or sodium amide as a base, the reaction is carried out in an anhydrous medium, for example anhydrous toluene,

-xylene, chlorobenzene, dimethylformamide and dimethylsulfoxyd. For example, 2.5 molar equivalents of the base are added to a well

stirred solution or suspension of a molar equivalent of dihydroxyanthraquinone (II) in an anhydrous solvent, after which the mixture is heated to form a diphenoxide of (II). In the case where sodium methoxide is used, the methanol which is released during the formation of diphenoxide is usually removed by azeotropic distillation.

About. 2.5 molar equivalents of the halogen compounds (VIII), (III) or (VI) are then added and the mixture obtained is heated to a temperature which can vary from 60° C to 150° C, depending on the type and boiling point of the solvent used. The reaction time can vary from 3 hours to 24 hours. The product obtained can be isolated by any suitable means, such as extraction or filtration. The bis-basic ether products are usually isolated as the bis-acid addition salts.

In methods where an alkali hydroxide is used as a base, such as sodium or potassium hydroxide, several different methods can be used. In one method, approx. 2.5 molar equivalents of a concentrated aqueous or methanolic solution, containing 25 - 50% of the alkali hydroxide, to a suspension of one molar equivalent of dihydroxyanthraquinone (II) in a suitable aromatic solvent, such as xylene or chlorobenzene. Under effective stirring, the mixture is heated to boiling whereby water or methanol is gradually removed by azeotropic distillation. If necessary, more of the aromatic solvent can be added during the distillation process to keep the volume of the mixture more or less constant. At the end of the distillation phase, the essentially anhydrous mixture contains the diphenoxide of (II), suspended in the aromatic solvent. About. 2.5 molar equivalents of the halides (VIII), (III) or (VI) are then added and the reaction is completed as described above.

In another method, one molar equivalent of dihydroxyanthraquinone (II) is dissolved in an aqueous solution of 2 molar equivalents of the alkali hydroxide. The solution obtained is filtered to remove any water-insoluble material, after which the solution is evaporated to dryness in a rotary evaporator. The solid diphenoxide of (II) is then washed with acetone, filtered and ground to a fine powder and further dried in a vacuum oven at approx. 100° C. The dry, solid diphenoxide is suspended in a suitable aromatic solvent, such as xylene or chlorobenzene, or an aprotic solvent such as dimethylformamide, after which the solution is heated under reflux with effective stirring. About. 2.5 molar equivalents of the appropriate halide (VIII), (III) or (VI) are added and the reaction is completed, as described above.

In a third method, the reaction is carried out in a heterogeneous medium consisting of water and an aromatic hydrocarbon, such as toluene and xylene. For example, a molar equivalent of dihydroxyanthraquinone (II) is suspended in an aromatic hydrocarbon. A resolution of approx. 2.5 molar equivalents of a hydrogen halide salt of the amine halide (VIII), dissolved in a minimal volume of water, are then added. During efficient stirring, add approx. 5 molar equivalents of a 25 - 50% aqueous solution of the alkali hydroxide, after which the mixture is heated under reflux for a period of 6 - 24 hours. The product formed can then be isolated from the hydrocarbon layer. If this method is used with the halides (III) or (VI), 2 molar equivalents of an aqueous solution of the alkali hydroxide are added to the well-stirred suspension of 1 molar equivalent of dihydroxyanthraquinone (II) in the aromatic hydrocarbon. About. 2.5 molar equivalents of the halides (III) or (VI) are then added to the mixture which is heated under reflux, and the reaction then proceeds to completion.

Water can be used as a reaction medium when using the reaction routes whereby the halides (III) or (VI) are used. For example, one molar equivalent of dihydroxyanthraquinone (II) is dissolved in an aqueous solution containing 2 molar equivalents of an alkali hydroxide. The solution is heated and, with rapid and effective stirring, a large excess of the halides (III) or (VI) is added. The mixture is then heated and processed as previously described.

The reaction between bis-(&)-halogeno-alkoxy)-anthraquinone (IV) and the amine (V) can be carried out under different conditions. For example, the bis-haloalkyl ether (IV) can be heated together with a large excess of the amine (V), where the excess amine serves both as a reaction medium and as a hydrogen halide acceptor. The reaction can be carried out at the boiling point of the amine, or in the case where a low-boiling amine is used, under pressure at temperatures above the boiling point of the amine; or one molar equivalent of the bis-haloalkyl ether (IV) and 4 or more molar equivalents of the amine (V) can be heated together in one or more different types of solvents, for example aromatic hydrocarbons, benzene, toluene or the like, or alcohols, such as methanol, ethanol or isopropanol, or aliphatic ketones such as acetone or butanone, or ethers such as tetrahydrofuran or dioxane. In some cases it may be advantageous to use only 2 molar equivalents of the amine (V) for each molar equivalent of the bis-haloalkyl ether (IV), together with an excess of powdered sodium or potassium carbonate, which serves as an acceptor for it formed hydrogen halide.

If the halogen atom in the bis-haloalkyl ether (IV) is either chlorine or bromine, the reaction between (IV) and the amine (V) is promoted by sodium or potassium iodide, which is added to the reaction mixture either in catalytic amounts or stoichiometric amounts.

Another method for the preparation of bis-basic ethers of 2,6- and 2,7-dihydroxyanthraquinones, represented by formula I, is shown by the following reaction core:

If the starting material is a bis-(w-alkylaminoalkoxy)-anthraquinone, i.e. R<3> = H; R<4> = alkyl, which can be prepared in a process shown later, this bis-secondary amine can also be alkylated with a suitable alkyl halide to give bis-tertiary amines in which both R<3> and R<4> are alkyl groups, which may be the same or different. Alkylation of such a bis-(u-alkyl-aminoalkoxy)-anthraquinone with formaldehyde and formic acid gives bis-3 4

tertiary amines, in which R = methyl and R = alkyl which may be the same or different from methyl. As can be seen, these methods are suitable methods for the production of bi-tertiaries

3 4

amines where R and R are two different alkyl groups.

The following examples illustrate the invention: Example 1

2, 6- bis[ 2-( diethylamirio)- ethoxyl- anthraquinone- dihydrochloride

To a solution of 12 g (0.3 mol) of sodium hydroxide

in 15 ml of water is added with efficient stirring to a boiling mixture of 36 g (0.15 mol) 2,6-dihydroxyanthraquinone suspension

there in 250 ml xylene. Under continuous stirring, the mixture was

gen heated under reflux and the water removed from the mixture by collection in a Dean-Stark distillation receiver. When all the water had been removed, a solution of 2-diethylaminoethyl chloride in 250 ml of xylene was added. This solution was prepared by dissolving 100 g (0.58 mol) of 2-diethylaminoethyl chloride tydrolcljDrid in 20 ml of water, covering the solution with 200 ml of xylene, cooling the mixture to approx. -5° C, and with rapid stirring add a solution of 45 g of potassium hydroxide in 35 ml of water. The xylene layer was decanted from the thick solution of inorganic salts in water, which was washed

ket with a further 50 ml of xylene. The combined xylene extracts were dried over anhydrous magnesium sulfate and filtered. With continued stirring, the resulting mixture was heated under reflux for a further 28 hours. The mixture was held for 500

ml of water and the yellow solid separated by xylene/

water liquid separation was removed by filtration under suction, carefully washed with hot water and dried. The bulk of the free base, m.p. 177-180°C, was recrystallized from a mixture of hot methanol and a small volume of chloroform to give the pure base, m.p. 179 - 180° C. A further 5 - 10% of the base can be obtained by working up the xylene layer.

The pure base was dissolved in chloroform and the solution acidified to Congo red with an ethereal hydrogen chloride solution, diluted with ether and the yellow precipitate filtered under suction. The resulting dihydrochloride salt was suspended in boiling methanol (15-20 ml per g) and a very small volume of water was added to promote dissolution. This solution was filtered,

evaporated to approx. 1/4 of the original volume, diluted

with the addition of methanol and then cooled. The recrystallized dihydrochloride was filtered and dried in a vacuum oven at 100° C. It melted with cleavage at 274 - 275° C.

(Or lower if the heating rate of the capillary tube was

slower) / X (H-,0) 272, E1, % 863.

max 2 members

Example 2

2, 6- bis- 2-( diethylamino)- ethoxy- arithraquinone- dihydrochloride

In addition to the method as indicated in example 1, this compound was also prepared by the following method. Under effective stirring, 100 g (0.42 mol) of 2,6-dihydroxyanthraquinone was dissolved in 500 - 700 ml of an approx. 10% solution of potassium hydroxide. The solution was filtered to remove small amounts of insoluble material, then evaporated to dryness in a rotary evaporator. The reddish-brown solid was dried in an oven at 100° C, ground to a fine powder, and redried at 100° C. The dry dipotassium diphenoxide weighed 10 - 25% more than the theoretical yield (132 g in this case), the excess weight being attributed to the amount of the potassium hydroxide used. This amount of diphenoxide was sufficient for several preparations as described below.

A stirred suspension of 30 g of the powdered diphenoxyd, containing approx. 24 g (0.075 mol) of the dipotassium salt of 2,6-dihydroxyanthraquinone in 200 ml xylene was heated under reflux and a small amount of water collected in a Dean-Stark distillation receiver. A solution of 2-diethylaminoethyl chloride in 100 ml of xylene, prepared according to Example 1 from 50 g (0.29 mol) of 2-diethylaminoethyl chloride hydrochloride was then added and the resulting mixture heated under reflux for 24 hours. The reaction mixture was then poured into water and worked up in the same way as indicated in example 1.

Similarly, the following bis-basic ethers of 2,6-dihydroxyanthraquinone and two bis-basic ethers of 2,7-dihydroxyanthraquinone were prepared:

Example 3

2,6-bis[2-(diethylamino)-ethoxyj-anthraquinone

In addition to the methods shown in examples 1 and 2, have

The following methods also proved useful. To a mixture of 114 g (0.6 mol) of 2,6-dihydroxyanthraquinone and 1.2 liters of chlorobenzene was added a solution of 412 g (2.4 mol) of 2-diethylaminoethyl chloride hydrochloride in 350 ml of water. With effective stirring, a solution of 264 g (4.0 mol) of potassium hydroxide pellets was obtained

(85%) in 350 ml of water added. The resulting mixture was heated with continuous stirring on a steam bath for 24 hours, then cooled by the addition of ca. 500 g of ice. 400 ml of chloroform was added. The underlying organic layer was separated and washed several times with water and then dried over anhydrous magnesium sulfate. After filtration, the solvent was removed under reduced pressure in a rotary evaporator. The residue was recrystallized from a mixture of methanol and chloroform,

as described in Example 1, and 2,6-bis-2-(di-ethylamino)-ethoxyanthraquinone base was obtained, m.p. 178 - 181° C. The base can be converted to the dihydrochloride salt, as described in example 1.

Example 4

2, 6- bis[ 2-(dimethylamino)- ethoxyj- anthraquinone- dihydrochloride

A well-stirred solution of 12 g (0.05 mol) 2,6-di-hydroxy-anthraquinone, 400 ml chlorobenzene, 50 ml methanol and 5.4 g (0.10 mol) sodium methoxide was heated to boiling and the methanol distilled from the mixture. When the boiling point of the distillate had reached 130° C, the mixture was allowed to cool to below 100° C. A solution of 2-dimethylaminoethyl chloride in 200 ml of chlorobenzene, prepared from 43.2 g (0.30

mol) 2-dimethylaminoethyl chloride hydrochloride, and the resulting solution refluxed with stirring for 24 hours. After cooling, the mixture was poured into 400 ml approx. 1% sodium hydroxide solution. The aqueous layer was extracted with chloroform. The combined organic fractions were washed well with water, dried over anhydrous magnesium sulfate, filtered and the solvent removed under reduced pressure in a rotary evaporator. The residue was dissolved in isopropanol and the solution acidified to Congo red by adding an ethereal solution of hydrogen

chloride. The dihydrochloride salt obtained was recrystallized from isopropanol and the pure compound was obtained, m.p. 278 - 280° C (decomposition). X , (H00) 273 mji, E*% 967.

maJcs i- lem Example 5

2, 7- bis[ 2-( dimethylamirio)- ethoxy}- anthraquinone- dihydrochloride

This compound was prepared according to Example 4 from 2,7-dihydroxyanthraquinone, with the exception that chlorobenzene was replaced by toluene as the reaction medium. The dihydrochloride salt was recrystallized twice from butanone with enough methanol added to achieve resolution. The isolated product was a hemihydrate, sm•i .pn . 230 - 233° C (decomposition<g>); X mcU, cs (95% ethanol) 273 y, E^<*>m 1150.

Example 6

2„ 6-bis(2-morpholinoethoxy)-anthraquinone- dihydrochloride

This compound was prepared according to the procedure shown in Example 3, with the exception that toluene was used as reaction medium instead of chlorobenzene, from 36 g (0.15 mol) of 2,6-dihydroxyanthraquinone, 100 g (0.54 mol) N-(2-chloroethyl)-morpholine hydrochloride, 66 g (1.0 mol) potassium hydroxide pellets (85%), 400 ml toluene and 100 ml water. The dihydrochloride salt was recrystallized twice from isopropanol with sufficient water added to promote dissolution. The pure compound melted with cleavage at 288-290°C, X (H.,0) 273 my, ET* 778 .

limb

Example 7

2, 6- bis[ 3- diethylamino)- propoxy]- anthraquinone- dihydrochloride

A mixture of 12 g (0.05 mol) of 2,6-dihydroxyanthraquinone, 16.5 g (0.11 mol) of 3-diethylaminopropyl chloride, 48 ml of 10% sodium hydroxide solution and 100 ml of dimethyl sulfoxide was stirred and heated on a steam bath for 2 hours. After cooling, the mixture was held for approx. 500 ml of water. The solid that precipitated was filtered off under suction and washed with water. The impure wet solid was dissolved in chloroform. The solution was dried over anhydrous magnesium sulfate, filtered and the filtrate acidified to Congo red with an ethereal solution of hydrogen chloride. After dilution with anhydrous ether, the yellow solid was filtered off and stirred. After two recrystallizations from 95% ethanol, the dihydrochloride (a hydrate) melted with decomposition at 273.5 - 274.5° C, <X>max (HjO) , 27<4.><E>^m 761.

Example 8

Using the procedure of Example 4, but replacing 2,7-dihydroxyanthraquinone with 2,6-dihydroxyanthraquinone, and replacing 2-dimethylaminoethyl chloride with the appropriate molar equivalent amount of either 3-dimethylaminopropyl chloride, 3-diethylaminopropyl chloride, 2 -diisopropylamino-ethyl chloride, N-(2-chloroethyl)-<p>yrrolidine or N-(2-chloroethyl)-morpholine, the following five compounds were also prepared: 2,7-bis[3-(dimethylamino)-propoxyj anthraquinone -dihydrochloride, 2,7-bis[3-(diethylamino)-propoxy]anthraquinone dihydrochloride, 2,7-bis[2-diisopropylamino)-ethoxy]anthraquinone dihydrochloride, 2,7-bis(2-pyrrolidinoethoxy)-anthraquinone dihydrochloride and 2,7-bis(2-morpholinoethoxy)-anthraquinone dihydrochloride.

Example 9

2,6-bis-2-(ethylamino)-ethoxy-anthraquinone

A mixture of 9.0 g (0.025 mol) of 2,6-bis-(2-chloro-ethoxy)-anthraquinone, 4.0 g of potassium iodide, 30 ml of 70% strength aqueous ethylamine and 100 ml of tetrahydrofuran is heated with stirring at 125 ° C for 20 hours, in an autoclave. The reaction mixture is evaporated to dryness in a rotary evaporator, diluted with water, acidified to Congo red with hydrochloric acid and the resulting mixture filtered or extracted with chloroform to remove unreacted starting material. The aqueous layer is made alkaline with a 10% sodium hydroxide solution and the mixture is extracted with chloroform. The chloroform extract is washed with water, dried over anhydrous magnesium sulphate, filtered and the chloroform is evaporated. The 2,6-bis[2-(ethylamino)-ethoxy]-anthraquinone base can be converted to the dihydrochloride salt, as previously described, for example in example 1. In the same way, 2,7-bis[2-(ethylamino)-ethoxy] -anthraquinone is produced from 2,7-bis-(2-chloroethoxy)-anthraquinone.

In the compounds produced according to the present invention, the basic ether groups are in positions that are separated from the carbonyl groups with the anthraquinone nuclei by at least 2 ring carbon atoms and the aforementioned basic ether groups are found in separate benzoid rings. It has been found that such compounds have an unexpectedly surprising antiviral activity and strong effect, especially by oral administration, compared to similar types of bis-basic ethers of dihydroxyanthraquinones, in which the basic ether groups are present in positions separated from the carbonyl groups, in the anthraquinone nucleus , with only one ring carbon atom. ■ Compounds of the latter type are described, for example, in US patent no. 2,881,173, as exhibiting anthelmintic and antiprotozoan activity. When prepared and examined under comparative experimental conditions, it has not been found that the bis-basic ethers of dihydroxyanthraquinones, according to the aforementioned US patent, exhibited any effective antiviral activity and powerful effect, while the bis-basic ethers of dihydroxyanthraquinones, prepared according to present invention, was found to exhibit remarkable efficacy and superior antiviral activity and potency.

The compounds according to the present invention were investigated and have been found to exhibit an unexpectedly surprising antiviral activity and powerful effect against infections by arboviruses, e.g. Semliki Forest and Vesicular Stomatitis, myxovirus, e.g. influenza A Equine/New Mex., poxvirus, e.g. Vaccinia IHD, pivorna virus, e.g. Mengo and herpes viruses, eg Herpes Simplex.

Claims (3)

1. Analogous procedure for the preparation of an antiviral compound of the general formula or a pharmaceutically acceptable acid addition salt thereof, wherein R 1 and R 2 , which are never the same, are hydrogen or the group wherein A is a straight chain alkylene group of 2 or 3 carbon atoms, and each R * 5 and R A is hydrogen, an alkyl group of 1- 3 carbon atoms, or R 3 and R 4 together with the nitrogen atom to which they are attached, form a pyrrolidine, piperidine or morpholine ring, characterized in that A) a compound of the formula where the hydroxyl groups are in 2,6- or 2,7- the positions, is reacted with a compound of the formula in the presence of a base, and where X is a reactive halogen and R "3, R<4> and A have the previously indicated meanings, B) a compound of formula II is first reacted with a compound of the formula and the reaction product is then reacted with a compound of the formula where R 3 , R 4 , A and X have the meanings given above, C). a compound of formula II is first reacted with a compound of formula and that the reaction ion product is then reacted with SOC^/ SOB^z HC1 or HBr, after which the reaction product of this reaction is reacted with a compound of the formula where R<3>, R<4>, A and X have the meanings given above, and if desired the base of formula (I) is converted into a pharmaceutically acceptable acid addition salt by reaction with a pharmaceutically acceptable acid. 2. Analogous method according to claim 1 for the production of 2,7-bis[2-(diethylamino)ethoxy]-anthraquinone, characterized in that 2,7-dihydroxyanthraquinone is reacted with 2-diethylaminoethyl chloride. 3. Analogous method according to claim 1 for the production of 2,6-bis-(2-piperidinoethoxy)-anthraquinone, characterized in that 2,6-dihydroxyanthraquinone is reacted with N-(2-chloroethyl)-piperidine.